This disclosure generally relates to microtablets for drug delivery and to methods of making microtablets which comprise a drug. In particular, the disclosure relates to methods for making microtablets in a process that is readily scalable and that produces consistent microtablets.
Solid forms of drug may be desirable for many reasons, including formulations with low moisture content that allow increased in vivo drug stability in implantable drug delivery systems, and the ability to provide highly concentrated drug formulation, which may be required for small implants (which need an efficacious drug payload in a small volume). However, the preparation and handling of small amounts of drug can present challenges in maintaining consistency and reproducibility of the drug formulation.
U.S. Patent Application Publication No. 2004/0146434, published on Jul. 29, 2004, and Kane et al., JALA 9(4): 218-227, published August 2004, describe one example of methods and systems for the preparation and handling of small amounts of solids, which generally involves forming a powder bed, inserting a tube into the powder bed to obtain a “plug” of powder, removing the tube from the bed, and ejecting the plug of powder. (See Kane et al., and FIG. 1 of this patent application). Such prior art methods, however, may suffer problems, including difficulty reproducibly forming small amounts of solids having consistent therapeutic dosages. Numerous factors contribute to these difficulties, including non-homogeneous/non-uniform powder beds, powder bed integrity during the coring process, changing powder bed boundary conditions due to adjacent coring, inefficient use of the formulation (e.g., only ˜50% of powder bed surface area can be cored), and deleterious effects (on both powder properties {flow properties, density, compressibility, agglomeration} and drug stability) of recycled powder beds and/or previously compressed powder beds on formation of subsequent plugs. One of the smallest tableting dosage forms available using commercially available equipment is provided by Colorcon Inc. Mini-Tabs are ˜2 mm in diameter and can be enterically coated using perforated pan or fluid bed coating technology.
A method for manufacturing tablets smaller than 1-2 mm, with good reproducibility and content uniformity, has not yet been achieved. Furthermore, tableting biomolecules (regardless of tablet size) using conventional techniques without the loss of activity is not readily achievable.
Thus, a need exists for methods and systems for making microtablets of solid drug formulations for drug delivery that desirably overcome one or more of the foregoing problems associated with prior methods. There also is a need for such a process that can be scaled to increase production of microtablets without deleterious effects on the product specifications, such as content uniformity.